Objective: Evaluate the efficacy and safety of losmapimod for the treatment of FSHD.
Background: FSHD is a chronic, variably progressive disease leading to accumulation of disability over decades. Nonclinical studies have shown that losmapimod (a small molecule p38 α/β MAPK inhibitor) reduces the aberrant expression of DUX4, the underlying cause of FSHD. Two Phase 2 clinical studies, a 48-week randomized controlled study (ReDUX4, FIS-002-2019) and a 52-week open-label study (OLS, FIS-001-2019) demonstrated evidence of benefit of treatment with losmapimod on muscle structure and function, as well as FSHD-relevant clinical endpoints that are recognized by patients and favorable safety and tolerability, supporting continued development.
Fulcrum is initiating a Phase 3 double-blind, placebo-controlled trial to support the development of losmapimod in FSHD.
Methods: Approximately 230 people with FSHD, 210 with genetically confirmed FSHD1 and 20 with FSHD2, will be randomized 1:1 to receive losmapimod or placebo orally, twice daily for 48-weeks. The primary endpoint is reachable workspace quantification of total relative surface area (Q1-Q5) with 500 g wrist weight in the dominant arm, with secondary efficacy endpoints of quality of life in the neurological disorders upper extremity scale (Neuro-QoL UE), patient global impression of change (PGIC), and muscle fat infiltration (MFI) using whole-body musculoskeletal MRI (WB-MSK MRI). Exploratory assessments include muscle fat fraction, muscle strength by hand-held dynamometry, and patient reported outcomes (PRO) including patient global impression of severity (PGIS), a novel FSHD PRO, numeric pain rating scale (NPRS), 5-level EQ-5D (EQ-5D-5L) and healthcare utilization questionnaire.
Results and Conclusions: The design of this Phase 3 study will be presented.